Mast Cell Tumours

Mast cell tumours are a rare group of diseases that is caused by the accumulation of mast cells in tissues and organs. Mast cells are a type of white blood cell in the immune system that mediate inflammatory responses, such as allergic reactions.

Mast cell tumours are slightly more common in females, however anyone can develop this disease. The average age of diagnosis varies by subtype.

Types of Mast Cell Tumours

There are several types of mast cell tumours, which are often categorised by their location and presentation in the body.

Cutaneous Mastocytosis

Cutaneous Mastocytosis are mast cell tumours that are found in the skin. This disease is generally found in children under two, and often has a good prognosis. In some cases, cutaneous Mastocytosis may recur or develop into systemic Mastocytosis. Cutaneous Mastocytosis are thought to be benign conditions, but they can become malignant if left untreated.

Solitary Cutaneous Mastocytoma

A solitary cutaneous mastocytoma is a common form of cutaneous Mastocytosis that appears on the skin as a singular lesion. It resembles a persistent insect bite in appearance, and is most commonly found in infants less than three months old. Solitary cutaneous mastocytomas generally have an excellent prognosis.

These tumours can be further described by their shape:

  • Macule (maculopapular cutaneous Mastocytosis).
  • Plaque (plaque-type mastocytoma – rare).
  • Nodular mastocytoma (very rare).

Maculopapular Cutaneous Mastocytosis

Maculopapular cutaneous Mastocytosis, also known as urticaria pigmentosa, is the most common type of cutaneous Mastocytosis. They generally occur in infants around three to four years old, however they can be found in adults. In children, Maculopapular cutaneous Mastocytosis can go away on their own, and often have a good prognosis. Adults who develop this condition may go on to have a systemic Mastocytosis.

Diffuse Cutaneous Mastocytosis

Diffuse cutaneous Mastocytosis is a rare form of cutaneous Mastocytosis that appears as a diffuse redness of the skin (or erythroderma) with various degrees of blistering. It is most commonly found in infants under the age of two, however adults and adolescents can also develop the disease. Diffuse cutaneous Mastocytosis is not usually aggressive, and can have a good prognosis.

Telangiectatic Cutaneous Mastocytosis

Telangiectatic cutaneous Mastocytosis, also known as telangiectatic macularis eruptive perstans (TMEP) is a very rare form of cutaneous Mastocytosis that is characterised by small, irregular spots and brown, widened blood vessels (or telangiectasia) on the trunk, arms and legs. Unlike most forms of cutaneous Mastocytosis, this disease is more common in adults, and may not have as good of a prognosis as other subtypes.

Systemic Mastocytosis

Systemic Mastocytosis are mast cell tumours that develop in extracutaneous tissue (or outside of the skin). This disease is generally found in adults, and are generally more aggressive than cutaneous Mastocytosis. Many types of systemic Mastocytosis are benign, however, some are malignant.

Indolent Systemic Mastocytosis

Indolent systemic Mastocytosis is the most common type of systemic Mastocytosis, and is the least aggressive. Unlike other subtypes of this disease, indolent systemic Mastocytosis can affect the skin, and may have maculopapular skin lesions. This disease can have a good prognosis when caught early.

Rare subtypes of indolent systemic Mastocytosis include:

  • Isolated bone marrow Mastocytosis.
  • Well-differentiated Mastocytosis.

Smouldering Systemic Mastocytosis

Smouldering systemic Mastocytosis is a less common form of systemic Mastocytosis, and generally have more groups of mast cells present. This disease can affect the bone marrow, and can cause enlargement of the spleen and/or the liver. Smoldering systemic Mastocytosis tends to be more aggressive, and may not have as good of a prognosis as other mast cell tumours.

Aggressive Systemic Mastocytosis

Aggressive systemic Mastocytosis is a rare and highly aggressive disease that causes an impairment or loss of organ function due to mast cell clusters. This disease is most commonly found in people over 60, and tends to be very aggressive. Aggressive systemic Mastocytosis may not have as good of a prognosis as other mast cell tumours.

Systemic Mastocytosis with an Associated Hematologic Neoplasm

Systemic Mastocytosis with an associated hematologic neoplasm occurs when a patient meets the criteria for systemic Mastocytosis, as well as a hematologic neoplasm. In most cases, the associated condition is either myeloproliferative neoplasms (MPNs) or Myelodysplastic syndromes (MDSs).

For more information on MPNs and MDSs, please refer to the Rare Cancers Australia KnowledgeBase.

Mast Cell Leukaemia

Mast cell leukaemia (MCL) is a very rare and very aggressive subtype of systemic Mastocytosis. MCL occurs when abnormal mast cells invade the bone marrow, and begin to circulate through the blood. This disease is likely to metastasise, and may not have as good of a prognosis as other mast cell tumours.

Mast Cell Sarcoma

Mast cell sarcomas are a very rare and very aggressive disease that is not classified as a cutaneous or systemic form of Mastocytosis. They are solid tumours that arise from mast cells infiltrating bone and soft tissue. This disease is likely to metastasise, and may not have as good of a prognosis as other mast cell tumours.

Treatment

If a benign mast cell tumour is detected, it will not require staging unless it progresses into an advanced disease.

If a malignant mast cell tumour is detected, it will be staged and graded based on size, metastasis,and how the cancer cells look under the microscope. Staging and grading helps your doctors determine the best treatment for you.

Cancers can be staged using the TNM staging system:

  • T (tumour) indicates the size and depth of the tumour.
  • N (node) indicates whether the cancer has spread to nearby lymph nodes.
  • M (metastasis) indicates whether the cancer has spread to other parts of the body.

This system can also be used in combination with a numerical value, from stage 0-IV:

  • Stage 0: this stage describes cancer cells in the place of origin (or ‘in situ’) that have not spread to nearby tissue.
  • Stage I: cancer cells have begun to spread to nearby tissue. It is not deeply embedded into nearby tissue and had not spread to lymph nodes. This stage is also known as early-stage cancer.
  • Stage II: cancer cells have grown deeper into nearby tissue. Lymph nodes may or may not be affected. This is also known as localised cancer.
  • Stage III: the cancer has become larger and has grown deeper into nearby tissue. Lymph nodes are generally affected at this stage. This is also known as localised cancer.
  • Stage IV: the cancer has spread to other tissues and organs in the body. This is also known as advanced or metastatic cancer.

Cancers can also be graded based on the rate of growth and how likely they are to spread:

  • Grade I: cancer cells present as slightly abnormal and are usually slow growing. This is also known as a low-grade tumour.
  • Grade II: cancer cells present as abnormal and grow faster than grade-I tumours. This is also known as an intermediate-grade tumour.
  • Grade III: cancer cells present as very abnormal and grow quickly. This is also known as a high-grade tumour.

Once your tumour has been staged and graded, your doctor may recommend genetic testing, which analyses your tumour DNA and can help determine which treatment has the greatest chance of success. They will then discuss the most appropriate treatment option for you.

Treatment is dependent on several factors, including location, age, stage of disease and overall health.

Treatment for mast cell tumours may include:

  • Allergy medications, potentially including:
    • Antihistamines.
    • Epinephrine/Adrenaline (EpiPens).
    • Leukotriene antagonists.
    • Sodium cromoglycate.
    • H2 blockers.
    • Omalizumab.
  • Photodynamic therapy.
  • Proton pump inhibitors, potentially including:
    • Omeprazole.
    • Lansoprazole.
    • Pantoprazole.
  • Corticosteroids.
  • KIT inhibitors.
  • Targeted therapy.
  • Interferon therapy.
  • Chemotherapy.
  • Bone marrow transplant.
  • Stem cell transplant.
  • Clinical trials.
  • Palliative care.

Risk factors

Because of how rare mast cell tumours are, there has been limited research done into the risk factors of these diseases. However, a genetic mutation of the KIT gene has been confirmed as a risk factor.

Symptoms

Many people with a mast cell tumour may appear asymptomatic in the early stages of disease. As the tumour progresses, some of the following symptoms may appear.

Symptoms of Solitary Cutaneous Mastocytoma

Symptoms of a solitary cutaneous Mastocytoma may include:

  • A firm macule, plaque or node.
  • A lesion that is red, pink, yellow, or brown in colour.
  • Itching – especially when rubbed.
  • Darier sign (lesion that urticates or blisters after rubbing).
  • Skin flushing.

Symptoms of Maculopapular Cutaneous Mastocytosis

Symptoms of a maculopapular cutaneous mastocytoma in children may include:

  • Brown patches and abnormal freckles.
  • Darrier sign.
  • Blisters.

Symptoms of a maculopapular cutaneous mastocytoma in adults may include:

  • Abnormal-looking lesions.
  • Itchy lesions.
  • Flushing of the skin.
  • Hypotension.
  • Anaphylactic shock.
  • Diarrhoea.
  • Blood in stool.

Symptoms of Diffuse Cutaneous Mastocytoma

Symptoms of a diffuse cutaneous mastocytoma may include:

  • Erythroderma.
  • Widespread blistering of the skin.
  • ‘Leathery’ appearance and texture of the skin.
  • Darrier sign.
  • Itching.
  • Blistering.
  • Hypotension.
  • Diarrhoea.
  • Blood in stool.
  • Anaphylactic shock.

Symptoms of Telangiectatic Cutaneous Mastocytosis

Symptoms of a telangiectatic cutaneous mastocytoma may include:

  • Small, irregular spots on the skin.
  • Telangiectasia.

Symptoms of Indolent Systemic Mastocytosis

Symptoms of an indolent systemic mastocytosis may include:

  • Skin flushing.
  • Diarrhoea.
  • Skin lesions similar to those produced by a maculopapular cutaneous mastocytoma.
  • Splenomegaly.
  • Hepatomegaly.

Symptoms of Smouldering Systemic Mastocytosis

Symptoms of a smouldering systemic mastocytosis may include:

  • Splenomegaly.
  • Hepatomegaly.
  • Lymphadenopathy.
  • High levels of tryptase in the blood.
  • Abnormal level of mast cells in bone marrow.

Symptoms of Systemic Mastocytosis with associated haematological neoplasm

Symptoms of a systemic mastocytosis with an associated haematological neoplasm may include:

  • Splenomegaly.
  • Hepatomegaly.
  • Lymphadenopathy.
  • Abdominal pain.
  • Nausea and/or vomiting.
  • Headaches.
  • Dizziness.
  • Hypotension.
  • Flushing of the skin.

In addition to these symptoms, patients may also present with the symptoms of their associated condition.

Symptoms of Aggressive Systemic Mastocytosis

Symptoms of an aggressive systemic mastocytosis may include:

  • Organ dysfunction (symptoms vary based on organ affected).
  • Leukopenia.
  • Anaemia.
  • Thrombocytopenia.
  • Malabsorption of nutrients.
  • Skin flushing.
  • Hypotension.
  • Anaphylactic shock.
  • Diarrhoea.
  • Blood in stool.
  • High levels of tryptase in the blood.

Symptoms of Mast Cell Leukaemia

Symptoms of a MCL may include:

  • Weakness and/or fatigue.
  • Syncope.
  • Flushing of the skin.
  • Fever.
  • Tachycardia.
  • Unexplained weight loss/loss of appetite.
  • Diarrhoea.
  • Nausea and/or vomiting.
  • Itchiness.
  • Skin blisters.
  • Bone pain.
  • Hypotension.
  • Peptic ulcer disease.

Symptoms of Mast Cell Sarcoma

Symptoms of a mast cell sarcoma may include:

  • Flushing of the skin.
  • Fever.
  • Malaise.
  • Fatigue.
  • Tachycardia.
  • Mass in affected area.

Not everyone with the symptoms above will have cancer but see your general practitioner (GP) if you are concerned.

Diagnosis

If your doctor suspects you have a mast cell tumour, they may order the following tests to confirm the diagnosis and refer you to a specialist for treatment:

  • Physical examination.
  • Blood tests.
  • Imaging tests, potentially including:
    • Ultrasound.
    • Bone scan.
  • Bone marrow aspiration.
  • Biopsy.

References

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